生物谷：德國研究人員日前發(fā)現(xiàn)，一種名為“ＡＢＣＧ８”的基因發(fā)生變異可使人患膽結(jié)石的風(fēng)險(xiǎn)增加一倍,。
據(jù)德國媒體報(bào)道,，基爾大學(xué)研究人員約亨·漢普領(lǐng)導(dǎo)的科研小組發(fā)現(xiàn)，膽結(jié)石主要是由于膽汁中膽固醇或非結(jié)合膽紅素的含量過多造成,，而“ＡＢＣＧ８”基因控制著肝臟向膽道排放膽固醇的過程,。該基因的變異導(dǎo)致排放進(jìn)入膽道的膽固醇過多，從而導(dǎo)致膽結(jié)石風(fēng)險(xiǎn)增大,。
不過,，研究人員指出，雖然該基因與膽結(jié)石有一定關(guān)系,，但過度肥胖仍是與膽結(jié)石相關(guān)的最大健康威脅,。膽結(jié)石是發(fā)達(dá)國家中的常見疾病，發(fā)病率達(dá)１０％至２０％,。
該研究發(fā)表在英國《自然遺傳學(xué)》雜志網(wǎng)站上,。（新華網(wǎng)）
原始出處:
Nature Genetics
Published online: 15 July 2007 | doi:10.1038/ng2101
A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease
Stephan Buch1,2,3,13, Clemens Schafmayer3,4,13, Henry Völzke5, Christian Becker6,7, Andre Franke2, Huberta von Eller-Eberstein3, Christian Kluck6,7, Ingelore Bässmann6,7, Mario Brosch1, Frank Lammert8, Juan Francisco Miquel9, Flavio Nervi9, Michael Wittig2, Dieter Rosskopf10, Birgit Timm3, Christine Höll3, Marcus Seeger1, Abdou ElSharawy2, Tim Lu11, Jan Egberts4, Fred Fändrich4, Ulrich R Fölsch1, Michael Krawczak3,11, Stefan Schreiber2,3, Peter Nürnberg6,12, Jürgen Tepel4 & Jochen Hampe1
Abstract
With an overall prevalence of 10–20%, gallstone disease (cholelithiasis) represents one of the most frequent and economically relevant health problems of industrialized countries1, 2. We performed an association scan of >500,000 SNPs in 280 individuals with gallstones and 360 controls. A follow-up study of the 235 most significant SNPs in 1,105 affected individuals and 873 controls replicated the disease association of SNP A-1791411 in ABCG8 (allelic P value PCCA = 4.1 10-9), which was subsequently attributed to coding variant rs11887534 (D19H). Additional replication was achieved in 728 German (P = 2.8 10-7) and 167 Chilean subjects (P = 0.02). The overall odds ratio for D19H carriership was 2.2 (95% confidence interval: 1.8–2.6, P = 1.4 10-14) in the full German sample. Association was stronger in subjects with cholesterol gallstones (odds ratio = 3.3), suggesting that His19 might be associated with a more efficient transport of cholesterol into the bile.
First Department of Medicine, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Institute for Clinical Molecular Biology, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
POPGEN Biobank, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Department of General and Thoracic Surgery, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Institute for Community Medicine, University Hospital Greifswald, Walther Rathenau Str. 48, 17487 Greifswald, Germany.
Cologne Center for Genomics, University of Cologne, Zülpicher Strasse 47, 50674 Cologne, Germany.
RZPD German Resource Center for Genome Research, Heubnerweg 6, 14059 Berlin, Germany.
Department of Internal Medicine I, University Hospital Bonn, Sigmund Freud-Strasse 25, 53105 Bonn, Germany.
Departamento de Gastroenterologia, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Institute of Pharmacology, Ernst-Moritz-Arndt University Greifswald, Friedrich Loeffler Str. 23d, 17487 Greifswald, Germany.
Institute of Medical Statistics and Informatics, University Hospital Schleswig-Holstein, 24105 Kiel, Germany.
Center for Molecular Medicine Cologne (CMMC), University of Cologne, Joseph-Stelzmann-Strasse 52, 50931 Köln, Germany.
These authors contributed equally to this work.
Correspondence to: Jochen Hampe1 e-mail: [email protected]
